To Transfuse or Not to Transfuse That is the Question

To Transfuse or Not to Transfuse That
is the Question
Jordan Moskoff MD
Associate Medical Director Adult Emergency
Services Cook County Hospital(Stroger)
Assistant Professor Emergency Medicine
Rush Medical College

Transfusion Questions
Packed Red Blood Cells
– Septic ICU patients?
– Trauma and burns?
– Cardiac disease?
Fresh Frozen Plasma
– Central Line Placement?
– LP?
– Volume Expander?
Platelets
– Prophylactic?
– Bleeding?

What would you do
83 y/o female NHR with AMS
– HR 92, BP 82/46, RR 20, SaO2 98%
– PMH: Dementia, CAD
– EKG unchanged from previous
– Urine is cloudy
– Hb is 9.6g/dl down from 11.2g/dl 4 months
earlier.
34

Packed Red Blood Cells
Volume: 250 ml
Content: 200 ml Red Cells, 50 ml
Plasma, and Anticoagulant
One unit will raise Hemoglobin level
by 1 g/dl or hematocrit by 2-3% in
an average 70 kg adult

Transfusion Trigger
Historically Hemoglobin 10g/dl
Given limited resources and risks of
transfusion can this be safely lowered?
Should there be a transfusion trigger at
all?

Transfusion Trigger
– “No single criterion should be used as an
indication for red cell component therapy and
that multiple factors related to the patients’
clinical status and oxygen delivery needs
should be considered.”
-NIH consensus statement 1988

No Trigger then what...
When to transfuse?
– Symptoms of Anemia?
Easy fatigue
Dyspnea on exertion
tachycardia
– Volume Expansion?
– Improve oxygenation?
– Coronary Artery Disease?

The return of Transfusion Trigger
Hebert PC, Wells G, Blajchman MA, et al: A
multicenter, randomized, controlled clinical trial
of transfusion requirements in critical care. N
Engl J Med 1999; 340:409-417.

TRICC
(Transfusion Requirements in Critcal Care)
Examined liberal vs. Restrictive transfusion
strategy in ICU setting
– Randomized, prospective clinically controlled
trial
– Two arms
Hemoglobin 10g/dl – 12g/dl
Hemoglobin 7g/dl – 9g/dl
– Determine mortality at 30 days and 60 days

TRICC
Inclusion - Septic ICU patients
– Not actively bleeding
– Euvolemic
– No Acute Myocardial Infarction
– No Unstable Angina

Results
TRICC
– lower Mortality in restrictive group
– lower Cardiac Events (AMI) in
restrictive group
– lower ARDS in restrictive group
– lower Pulmonary Edema in
restrictive group

Conclusions:
TRICC
– New trigger is at 7 g/dl - it is safe to restrict.
“A restrictive strategy of red cell transfusion is at
least as effective as and possibly superior to a
liberal transfusion strategy in critically ill patients,
with the possible exception of patients with acute
myocardial infarction and unstable angina”
– Blood is bad
More transfusions = more mortality
12 13

Yep it’s true
Anemia and Blood Transfusion in Critical
Care (ABC study)
– Higher ICU and overall mortality rates in
patients who received blood transfusions than
those who had not.
CRIT study
– Independent direct relationship between the
number of transfusions received and longer
ICU and hospital length of stay as well as
increased mortality

How Can Something That Seems so
Good, Be So Bad?

Blood Transfusion Risks
1. Immunologic Reactions
2. Infectious Disease
3. Metabolic Derangements
4. Hypothermia
5. Coagulation Defects

Immunologic Reactions
1. Febrile Nonhemolytic
A. Most common transfusion reaction (1%)
B. Usually benign
C. Antipyretics

Immunologic Reaction
Should you pre-medicate with Tylenol and
Benadryl?
17 18

Immunologic reaction
Randomized, placebo controlled study showed no
efficacy of pre-medication (Wang, 2002)
18 19

Immunologic Reactions
2. Acute Hemolytic - incompatible blood
– A. Medical emergency (shock, ARF, DIC)
– B. RBC destruction due to ABO incompatibility
– C. Fever, chills, flank pain, pink urine, oozing
– D. Immediately stop transfusion and send blood to
lab
– E. Fluid resuscitation, vasopressors, supportive care
3. Allergic/Anaphylactic
– A. Mild: Histamine release causing urticaria
(Benadryl)
– B. Severe: Shock, angioedema, low BP, resp distress
– C. Occurs within minutes of starting transfusion
– D. Life threatening in 1:20,000 - 50,000 transfusions
19 20

Immunologic Reactions
4. Transfusion Related Acute Lung Injury (TRALI)
A. Incidence 1:2000, generally favorable prognosis
B. Leaky capillaries causes pulmonary edema, no
CHF
C. Diagnosis
– no radiographic infiltrates or hypoxia
– within 6 hours of transfusion
Treatment is aggressive pulmonary support

1. Viral Infection
Infectious Disease
A. Hepatitis B 1:31,000 to 81,000
B. Hepatitis C 1:1,900,000 to 3,100,000
C. HIV 1:2,100,000
D. HTLV 1:2,000,000
E. CMV screened for high risk recipients only
2. Risk of bacterial or syphilis infections very
low
3. West Nile Virus
4. Prion are rare

Metabolic Derangements
1. Transfusion Related Circulatory Overload (TACO)
A. Circulatory overload causing CHF (lung edema)
B. Pts with decreased cardiac function more at risk
C. Blood should be given slowly and sparingly
D. Treat with supplemental oxygen and diuretics
2. Citrate Toxicity
A. Decreased ionized Ca levels from citrate chelation
B. Rarely occurs except in severe liver disease or
massive transfusion > 10 units
C. Replace Ca PRN symptoms or serum levels

Metabolic Derangements
3. Metabolic Alkalosis
A. Cause is citrate metabolism to
bicarbonate
B. Massive transfusion, shock, renal disease
C. Hypokalemia can occur
4. Hyperkalemia
A. Rare except in pts with renal impairment
5. Iron Overload (Hemosiderosis)
A. Only occurs with chronic repeated
transfusions
B. Treatment is with iron chelation agents

Hypothermia
Occurs with rapid infusion of large volumes of cold blood
Can cause coagulapathy and cardiac arrhythmias
The danger is compounded in patients experiencing
shock or surgical/anesthetic manipulations that disrupt
temperature regulation
A commercially available blood warmer should be used in
the OR and SICU to help prevent this complication
Uncontrolled blood warming (IV bag or tubing in hot
water) can lead to excessive hemolysis

Coagulation Defects
Caused by the dilution effect of PRBC transfusion
(usually requires replacing at least 1-2 total blood
volumes to be significant)
10 units of PRBC’s transfused cause a 50% drop in the
Plt count
Significant thrombocytopenia (Plts < 50K) leading to an
increased risk of bleeding can occur after 20 units of
PRBC’s are given
Monitor PT/INR, PTT, and Plt counts closely in massive
transfusions
Replacement therapy not based on any formula but
rather on the clinical status of the patient

That can’t be it...
There are risks but it doesn’t explain the
30 day mortality.
26

Are the Red Cells alone?
Transfusion-related immunomodulation
(TRIM)
– mediated by donor white cells
– down regulate recipients immune function
– correlation with nosocomial infection
27

Try it again without the white
cells
What if we leukoreduce the blood? Will
there be a different outcome?
28

Leukoreduction
Hebert et. al looked at data retrospectivly
after universal leukoreduction of Canadian
blood supply.
Found a small but statically significant
decrease in mortality.
29 28

I’ve taken out the risk where is
the benefit?
Shouldn’t the liberal group have improved
mortality?
30

Why isn’t better to give blood?
31

More isn’t always better...
32

Does Blood Work?
Blood transfusions increase mixed oxygen
venous saturation but may have no effect
on tissue oxygenation.
Blood is not a Twinkie
33 30

Storage Effects
Average age of stored blood in the US is
21 days
– Erythrocyte 2,3-DPG levels decline
immediately and go to zero by 72 hours.
absorb oxygen in lungs but do not release oxygen
unless tissue oxygen tension very low.
34 31

Storage effects
– Lose ability to deform
can become trapped in microvasculature
35

Storage effects
– Become Nitric Oxide (NO) scavengers
vasoconstriction
36

So every time I give blood am I
Killing the patients?

Not if you give it to the right
patient
Stored blood doesn’t work as well
Risk of TRALI, TACO,TRIM
Risk of infection, metabolic derangements,
hypothermia and coagulation defects
Euvolemic, non-bleeding patients wait
until they get to 7g/dl.
38 33

What would you do
83 y/o female NHR with AMS
– HR 92, BP 82/46, RR 20, SaO2 98%
– PMH: Dementia, CAD
– EKG unchanged from previous
– Urine is cloudy
– Hb is 9.6g/dl down from 11.2g/dl 4 months
earlier.
39 4

But what about Rivers?
Early Goal Directed Therapy
– Transfusion trigger is Hb 10g/dl
– If the SvO2

TRICC vs. EGDT
If the patient is septic and the SvO2 is

Clinical practice guideline: Red blood cell
transfusion in adult trauma and critical care.
Critical Care Medicine. December 2009
During the first 6 hours of severe sepsis or septic shock
if SvO2 is

Burn and Trauma Patients
What if the patient is not actively bleeding
but is going to surgery? Or going to be
sent to the burn unit. Is it still safe to
transfuse at 7g/dl?
43 37

Wahl et.al American Journal of
Surgery
Used a restrictive strategy (trigger at Hb
7g/dl) unless the patient had severe
cardiovascular disease.
Conclusion: “restrictive transfusion in
trauma and burn patients is safe overall”
44 38

What would you do?
53 y/o female with UGIB
– HR 106, BP 130/87, SaO2 98%
– NG Lavage - Bright Red Blood
– EKG T-Wave inversion V4, V5, V6
– Denies Chest Pain
– Hemoglobin 9.6g/dl

What would you do?
62 y/o male with chest pain
– HR 87, BP 134/76, RR 20, SaO2 98%
– h/o stent placed 5 months ago
– pain relieved with NTG
– EKG: NSR no ST change, no T wave inversion
– Troponin - positive
– Hb 8.2g/dl
46

OK so what if they have heart
disease?
47 39

Gets a bit muddy...
Study-polooza
48

Anemia with a history of Heart
Disease
Is a low transfusion threshold safe in
critically ill patients with cardiovascular
disease?
Subgroup analysis of TRICC study with
known coronary artery disease but no
active disease
• Herbert P, et al: Is a low transfusion threshold safe in critically ill patients with cardiovascular
diseases? Critical care Medicine. Vol. 29, Issue 2(February 2001).
49 40

Anemia with a history of Heart
Disease
Subgroup of 257 patients with known CAD
– “No clinically important mortality differences
...with known coronary artery disease”
– No increase in new myocardial infarction in
restrictive group
Conclusion
– Hb 7g/dl is safe with h/o CAD
• Herbert P, et al: Is a low transfusion threshold safe in critically ill patients with cardiovascular
diseases? Critical care Medicine. Vol. 29, Issue 2(February 2001).
50 41

What about if having chest
pain?
Veterans affairs hospitals
Separated into 3 groups
– Mild anemia 10.4 g/dl - 11.5g/dl
– Moderate anemia 9.0 g/dl - 10.4g/dl
– Severe anemia

Anemia with Chest Pain
Conclusions:
– “Severely anemic (

Anemia and admitted with
diagnosis of AMI
Patient’s admitted with AMI >65 y/o
– retrospectively looked at patients who had
received transfusions
– determine cutoff where difference was seen in
mortality
Wu et al. Blood transfusions in elderly patients with acute myocardial infarction. N Engl J Med 345
1230-1236.2001
53 44

Outcome:
Anemia and AMI
– Hb > 12 g/dl = Worsened outcome
– Hb < 12 g/dl = Improved outcome
Conclusion: transfusion was beneficial in
elderly patients with AMI and Hb < 12g/d
Wu et al. Blood transfusions in elderly patients with acute myocardial infarction. N Engl J Med 345
1230-1236.2001
54

What about the big cardiology
studies?
Meta analysis of GUSTO IIb, Pursuit and PARAGON B
studies of patients with ACS
– 10% of patients enrolled received transfusions.
– adjusted and controlled for all the variables of
transfused vs. nontransfused
– end points were mortality and MI
Rao SV, et al. Relationship of blood transfusion and clinical outcomes in patients with acute
coronary syndromes. JAMA 292. 1555-1562.2004.
55 45

Conclusions:
ACS and transfusions
– “risk of 30-day mortality and death or MI...
was significantly higher in the transfused
group.”
– Below Hct 25% (Hb 7 g/dl) there was no
difference in mortality between the groups.
• Rao SV, et al. Relationship of blood transfusion and clinical outcomes in patients with acute
coronary syndromes. JAMA 292. 1555-1562.2004.
56

NSTEMI and transfusion
CRUSADE database
NSTEMI patients not undergoing cardiac
surgery.
transfusion was associated with death or
MI as an endpoint.
Yang et al. The implications of blood transfusions for patients with non-ST segment elevation
acute coronary syndromes: Results from the CRUSADE national quality improvement Initiative. J
Am Coll Cardiol 46, 1490-1495.2005
57 46

So what if they have an actual
STEMI
Meta analysis from 16 ACS studies
comparing patients with STEMI and
NSTEMI receiving transfusions.
Mortality was endpoint
Sabatine et al. Association of hemoglobin levels with clinical outcomes in acute coronary
syndromes. Circulation 111. 2042-2049. 2005
58 47

STEMI and NSTEMI
Patients with STEMI and Hb < 12g/dl had
better outcomes when transfused
Patients with NSTEMI had worse outcomes
when transfused no matter the initial Hb
Sabatine et al. Association of hemoglobin levels with clinical outcomes in acute coronary
syndromes. Circulation 111. 2042-2049. 2005
59

STEMI going to Cath lab
Retrospectively looked at patients who
went to cath for STEMI and recieved a
transfusion.
Conclusion: 90 day mortality worse if
received transfusion.
• Jolicoeur E: Transfusion and mortality in patients with ST-segment elevation myocardial infarction
treated with primary percutaneous coronary intervention. European Heart Journal. Vol. 30, Issue
21(November 2009).
60

What if they are going for
CABG?
Retrospective review of 12,000 patients
over 7 years CABG with transfusion vs.
CABG without transfusion
End point was mortality
Found increased 30 day mortality of
patients undergoing CABG who received
transfusion
Koch et al. Morbidity and mortality risk associated with red blood cell and blood-component
transfusion in isolated coronary bypass grafting. Crit Care Med 34. 1608-1616. 2006.
61 48

Cardiac Summary
Septic Patient with a History of ACS
No active Chest Pain
Safe to transfuse at 7g/dl
62 49

Cardiac Summary
Patient who is actively having chest pain
No changes on EKG, negative cardiac
markers
Safe to transfuse when Hb

Cardiac Summary
Patient with anemia and NSTEMI
Transfusions tend toward a worsening
mortality
Consider transfusion when Hb

Cardiac Summary
Patient with a STEMI who is going to the
cath lab
Transfusion tend to worsen mortality
Consider transfusion when Hb

Cardiac Summary
Perioperative CABG transfusions are
considered dangerous
Transfusion tend to worsen mortality
Consider transfusion when Hb

PRBC Conclusion
Transfusions have risks
Transfused blood doesn’t work that well
Transfusions may not increase Oxygen
tension in tissue
Without blood people die
67 50

PRBC Conclusion
Transfused Blood has risks and benefits
like all treatments.
As patients become more ill the benefits
begin to outweigh the risks.
It’s the best we have until we come up
with something else
68 51

Fresh Frozen Plasma

Volume: 200 ml
Fresh Frozen Plasma
Content: Normal Levels of All Coagulation Factors
Storage: 1 Year Frozen, After Thawing, 24 Hours
Dose: 15 ml/kg (Each Unit will Raise Plasma Factor
Activity Levels by 3-5%)

Fresh Frozen Plasma
Dose: Each unit will increase the level of any
clotting factor by 2-3 percent in an average
adult.
Jumbo Plasma: 400 to 600 ml/unit Prepared by
Plasma-Pheresis for exchange transfusion

FFP case
48 y/o female on Coumadin with INR 3.2
Needs central line placement for dialysis

Do you need to correct PT/PTT
prior to Central Line placement?
73

Placement of Central Venous
Catheters
Doerfler et al. 76 consecutive venous catheter placed in
patients with abnormalities of PT, PTT or both. There
were no serious complications.
Weigand et al. Prospective study in ICU with placement
of central venous catheters in patients with bleeding
abnormalities. No increased risk of bleeding.
Deloughery et al. Central venous catheters placed on
patients with coagulation deficits. Bleeding complications
secondary to experience of physician rather than
hemostatic deficits.
74 57

Placement of Central Venous
Catheters
Central venous catheters can be placed
safely in patients with coagulation
disorders. The risk of bleeding is related
only to the experience of the physician.
75 58

How about an LP?
76 59

Spinal epidural hematoma
Ruff et al. “anticoagulation and LP are
known to increase the risk of spinal
hematoma”
Roberts:Clinical Procedures in Emergency
Medicine
– “attempts should made to correct the clotting
deficiency if clinically feasible and time
permitting”
77 60

How about as Colloid?
56 y/o male alcoholic
– 80/40, 110, 32 SaO2 93% on NRB
– +JVD, Crackles to mid lung field, ascites,
edema
– No active bleeding
78 61

Not a volume expander
Marks et al. “Use of FFP... reserved for
patients with active bleeding, those
undergoing invasive procedures and those
at high risk of bleeding because of their
underlying diagnosis of associated
hematologic derangements”
79 63

FFP isn’t benign either
FFP causes TRALI, TACO and allergic
reactions.
Significant association between
transfusion of FFP and various infectious
complications
Soluble proteins in FFP may cause similar
immunosuppressive reactions as in PRBCs
- TRIM
80 62

Indications for Fresh Frozen Plasma
Reversal of Warfarin Effect with Bleeding
Congenital or Acquired Coagulopathy
– with Bleeding
Congenital or Acquired Coagulation Factor
Deficiency
Massive Blood Transfusion With Evidence of a
Coagulation Deficiency or Bleeding
For Active Bleeding or Prior to Emergency Surgery,
(PT>18 Seconds; INR >1.6)
Prior to Lumbar puncture
Plasma Exchange
– TTP, DIC

Platelets

Platelets (Random donor)
Volume: 50 ml
Content: > 5.5 X 1010 Platelets/Bag
Dose: 1 unit/10 kg Body Weight

Single Donor Platelets (Apheresis)
Volume: 200-600 ml
Content: >3 x 1011 Platelets/bag (Equivalent to
6-8 Units RDP)
Dose: One Apheresis Product/Transfusion
Episode

Platelets Case
47 y/o female with epistaxsis
Platelets 52,000

Platelets case
73 y/o with platelets of 8 no active
bleeding?
86 69

Deleterious effects
Transfusion-related acute lung injury (TRALI)
Increase in multi-organ failure and thrombosis
Down regulation of anti-tumor and anti-microbial
immunity

When to Transfuse
Platelet Count

Indications for Single Donor Platelets
(Apheresis)
To Control or Prevent Bleeding in
Thrombocytopenic Patients who are Refractory
to Random Donor Platelet Transfusions
Reduce Donor Exposures in Patients Receiving
Limited Number of Transfusions
(Transplantation)

Thank you
90

References
Hebert P, et al: A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care.
Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. NEJM. Vol. 340,
Issue 6(February 1999).
Harder L, et al: The Optimal Hematocrit. Critical Care Clinics. Vol. 26, Issue 2(April 2010).
Napolitano L, et al: Clinical practice guideline: Red blood cell transfusion in adult trauma and critical care. Critical
Care Medicine. Vol. 37, Issue 12(December 2009).
Tinmouth A et al: Blood conservation strategies to reduce the need for red cell transfusion in critically lll patients.
Canadian Medical Association Journal. Vol. 178, Issue 1(January 2008).
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Singla I, et al: Impact of Blood Transfusions in patients presenting with anemia and suspected acute coronary
syndrome. The American Journal of Cardiology. Vol. 99, Issue 8(April 2007).
Aronson D, et al: Impact of Red Cell Transfusion on Clinical Outcomes in Patients with Acute Myocardial
Infarction. The American Journal of Cardiology. Vol. 102, Issue 2(July 2008).

References
Jolicoeur E: Transfusion and mortality in patients with ST-segment elevation myocardial infarction treated with
primary percutaneous coronary intervention. European Heart Journal. Vol. 30, Issue 21(November 2009).
Wahl W et al: Restrictive red blood cell transfusion not just for the stable intensive care unit patient. American
Journal of Surgery. Vol. 195, Issue 6(June 2008).
Spiess B: Red Cell Transfusions and Guideliness: A work in Progress. Hematology/Oncology Clinics of North
America. Vol.21, Issue 1(February 2007).
Herbert P, et al: Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases? Critical
care Medicine. Vol. 29, Issue 2(February 2001).
McPherson and Pincus: Henry’s Clinical Diagnosis and Management by Laboratory Methods, 21st ed. W.B.
Saunders Company. 2006.
Critical Care Medicine. Vol. 38, Issue 3(March 2010). Netzer G, et al: TRALI, transfusion, and acute lung injury:
Synergy in action?
Ansell J, et al: Pharmacology and Management of the Vitamin K Antagonists. Chest. Vol. 133, Issue 6(June
2008).
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References
Marks P: Coagulation Disorders in the ICU. Clinics in Chest Medicine. Vol. 30, Issue 1(March 2009).
Argo C, et al: Blood Products, volume control and renal support in the coagulopathy of liver disease. Clinics in
Liver Disease. Vol. 13, Issue 1(February 2009).
Ahmed S, et al: Critical Care Issues in Oncological Surgery Patients. Critical Care Clinics. Vol. 26, Issue
1(January 2010).
Sarani B, et al: Transfusion of fresh frozen plasma in critically ill surgical patients is associated with an increased
risk of infection. Critical Care Medicine. Vol. 36, Issue 4(April 2008).
Roberts: Clinical Procedures in Emergency Medicine, 5th ed. Contraindications for Spinal Puncture. Saunders,
2009.
Ruff R, et al: Complications of lumbar puncture followed by anticoagulation. Stroke. 1981;12;879-881.
Bradley W, et al: Laboratory Investigations in Diagnosis and Management of Neurological Disease. Bradley:
Neurology in Clinical Practice, 5th ed. Butterworth-Heinemann, 2008.
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References
Deloughery T: Invasive line Placement in critically ill patients: do hemostatic defects matter? Transfusion. Vol.
36, Issue 9(September 1996).
Weigand K et al: Low levels of prothrombin time (INR) and platelets do not increase the risk of significant
bleeding when placing central venous catheters. Med Klin (Munich). Vol. 104, Issue 5(May 2009).
Doerfler M, et al: Central Venous Placement in Patients with Disorders of Hemostasis. Chest. Vol. 110, Issue
1(July 1996).
Lauzier F, et al: Fresh Frozen plasma transfusion in critically ill patients. Critical Care Medicine. Vol. 35, Issue
7(July 2007).
Wandt H, et al: A therapeutic platelet transfusion strategy is safe and feasible in patients after autologous
peripheral blood stem cell transplantation. Bone Marrow Transplant. Vol. 37, Issue 4(February 2006).
Slichter S: Platelet transfusion therapy. Hematology/Oncology Clinics of North America. Vol. 21, Issue 4(August
2007).
94 77